Biomarkers Research: research to aid the development of novel risk prediction tools
The identification and validation of biomarkers in drug discovery/development and in disease diagnosis, treatment, prognosis, and prevention play an essential role in therapeutic responses and treatment ouctomes. Biomarkers increase the success rate of drug development programmes and thereby accelerate the availability of new therapeutics. The analytical validation phase of biomarker development is characterized by analysis of the performance metrics of the biomarker to ensure that the test is reliable, reproducible and of adequate sensitivity and specificity. The objective of the group is to undertake Systematic, Investigative and Experimental (“SIE”) studies which:
- Develop new knowledge regarding the biomarkers which explain uncontrolled and severe asthma
- Inform the development of new biomarker devices and identify new populations for device use
This research theme/project has been prioritised by a group of professionals in the asthma field as an area of scientific uncertainty that cannot be readily resolved by a competent professional, with novel features. The R&D requirements have been met as follows:
|Objectives||To overcome the scientific challenge of new biomarker testing devices to ensure:
|Novelty or technical risks||This is deemed a novel project and the first of its kind in Singapore in relation to the modification and/or development of new biomarker devices for FeNO based on acquiring new knowledge in relation to use for non-specific respiratory symptoms|
|SIE Studies/experiments in field of science||SIE study conducted to develop new knowledge and test solutions for patients with non-specific respiratory symptoms:
The ongoing research activities of the biomarkers group include a series of planned activities to test or find out something that is not known or readily deducible in the field of biomarkers and severe asthma which will enable the group to develop novel devices and therapies. The following SIE studies identified by the group will provide outcomes that cannot be known or determined prior to the commencement of the study because the knowledge, information or experience to achieve the outcome is not reasonably available
Activity 1 (NSRS) Does FeNO (biomarker) predict response to ICS in patients with non-specific respiratory symptoms?
Patients presenting with non-specific respiratory symptoms currently have a one-size-fits-all approach, often involving the prescription of inhaled corticosteroids (ICS). However, not all patients respond to ICS in the same manner, as such the development of tools to identify those patients most likely to respond to ICS would minimise inappropriate treatment and limit side-effects and unnecessary healthcare costs
FeNO (fraction exhaled nitric oxide) is easily measured in routine clinical visits and showed potential as a biomarker for ICS responsiveness in small clinical trials. However, current technology for the measurement of FeNO is expensive and there is a need for an affordable technology to measure FeNO in primary care. Therefore, the NSRS (Non-Specific Respiratory Symptoms) project was initiated to develop an affordable and reliable FeNO measurement technology which can be implemented as part of routine primary care in Singapore.
In consultation with leaders in the field, a SIE study was conducted as a 6-week double-blind randomised placebo-controlled trial including undiagnosed patients, aged 18–80 years, with non-specific, persistent respiratory symptoms, across 26 primary care centres and hospitals in the UK and Singapore. The clinical trial phase of this project represents a huge undertaking for OPRI to ensure the proper conduct of the trial per protocol and ethical approval and ensuring sufficient numbers of patients were recruited and completed the trial. There are also technical uncertainties faced by the company in the effectiveness of the NIOX device in providing reliable FeNO measurement in the Singapore population.
This result shows that FeNO measurement provides an easy and non-invasive tool to assist physicians in making ICS prescribing decision for patients with non-specific respiratory symptoms. The result of this research was published in Lancet Respiratory Medicine (impact factor: 21.5).
In the next activity for this SIE study, we will be working with collaborators to develop a novel affordable tool for measurement FeNO in primary care. We will also attempt to create a device capable of utilising the processing power of the ubiquitous smartphone for FeNO measurement.
David B Price, et al. Fractional exhaled nitric oxide as a predictor of response to inhaled corticosteroids in patients with non-specific respiratory symptoms and insignificant bronchodilator reversibility: a randomised controlled trial. Lancet Respir Med 2017.
[PubMed] [Full Text]
Predictive value of FeNO in patients with non-specific respiratory symptoms: a randomised controlled trial.
Price D, Buhl R, Copland A, Freeman D, Godley C, et al.
Eur Respir J 2017; 50(suppl 61): PA3886. [Poster] [Full Text]